Search results for "Myeloid"

2015

AbstractTriggering receptor expressed on myeloid cells (TREM)-1 plays an important role in innate immune responses and is upregulated under infectious as well as non-infectious conditions. In addition, a soluble TREM-1 variant (sTREM-1) is detectable in sera or bronchoalveolar-lavage fluids from patients. Currently, various studies are difficult to compare, since the methods of detection by enzyme-linked immunosorbent assays (ELISA) vary among different research groups. In this study, we compared three different s-TREM-1 specific ELISAs and identified individual assay characteristics finding notable differences in sTREM-1 concentrations in part depending on the employed buffers. Investigati…

The immunosuppressive enzyme IL4I1 promotes FoxP3+regulatory T lymphocyte differentiation

2015

Abstract IL4I1 (interleukin-4-induced gene 1) is a phenylalanine oxidase produced mainly by APCs of myeloid origin, and converts phenylalanine (Phe) to phenylpyruvate, hydrogen peroxide, and ammonia. We have previously shown that IL4I1 is highly expressed by tumor-associated macrophages from various human cancers and facilitates immune evasion from the cytotoxic response in a murine tumor model. Indeed, IL4I1 inhibits T-cell proliferation via hydrogen peroxide toxicity on effector/memory T cells. Here, we explored the effect of IL4I1 on naive CD4(+) T-cell differentiation. We show that IL4I1 stimulates the generation of Foxp3(+) regulatory T (Treg) cells in vitro from human and mouse T cell…

Towards Adoptive Immunotherapy Using High Affinity T Cell Receptors

2003

The hdm2 oncoprotein is frequently overexpressed in a variety of human malignancies, including acute myeloid and lymphoblastic leukemia. Synthetic peptides representative of hdm2 sequences were tested for their binding to A2.1. HLA-A2.1. (/Kb)-Tg mice were immunized with A2.1-binding hdm2 peptides in order to induce A2.1-restricted and hdm2-specific CTL. A2.1-restricted CTL lines obtained from both A2.1 and HuCD8 × A2.1/Kb-Tg mice were able to recognize a synthetic 8-mer peptide representative of a N-terminal hdm2 sequence. These CTL were capable of recognizing and lysing Saos-2 cells transfected with the hdm2 gene as opposed to the parental cell line that lacks any detectable hdm2 expressi…

Chronic myeloid leukemia as second malignancy; restrospective multicentric study

2009

Chronic myeloid leukemia as second malignancy; a retrospective multicentrico study

2009

THE ANTINEOPLASTIC ROLE OF STAT5 INHIBITION IN BCRABL1-POSITIVE CELLS EXPOSED TO PIMOZIDE ALONE AND IN COMBINATION WITH DASATINIB AND PONATINIB

2021

EVEN though the last decades have seen the success of the targeted treatments for BCRABL1-positive Chronic Myeloid Leukemia (CML), with the outstanding achievement of placing selected patients into the so called treatment-free remission, a minor part of these subjects face TKI resistance and/or intolerance. Resistance is a challenging point in the clinical management of CML, occurring in approximately 10–20% of CML cases, due to several mechanisms, among which point mutations of the BCR‐ABL kinase domain, BCRABL overexpression or alternative splicing, sub-efficient plasma concentration of the inhibitor and abnormal drug efflux/influx. The Signal Transducer and Activators of Transcription (S…

An Adapted Gating Strategy Integrating a Myelomonocytic Window Is Necessary For Correct Flow Cytometric Diagnosis In a Large Proportion Of AML With M…

2013

Abstract Background Previously, it has been reported, that AML with mutated NPM1 is associated with a distinctive immunophenotype. In particular, low or absent expression of CD34 accompanied by high expression of CD33, and – at least in part of the cases - absence of HLA-DR expression was reported. CD45/side scatter (SSC) gating is widely used for the identification of blasts by flow cytometry (FC). Blast cell gates typically are defined by a low SSC and moderate CD45 expression. However, in a number of patients with NPM1mutation this typical blast cell gate comprises significantly lower blast percentages when compared to the morphological evaluation. In these patient samples a second popul…

Inhibition of Arginase 1 Liberates Potent T Cell Immunostimulatory Activity of Human Neutrophil Granulocytes

2021

Myeloid cell arginase-mediated arginine depletion with consecutive inhibition of T cell functions is a key component of tumor immune escape. Both, granulocytic myeloid-derived suppressor cells (G-MDSC) and conventional mature human polymorphonuclear neutrophil granulocytes (PMN) express high levels of arginase 1 and can act as suppressor cells of adaptive anti-cancer immunity. Here we demonstrate that pharmacological inhibition of PMN-derived arginase 1 not only prevents the suppression of T cell functions but rather leads to a strong hyperactivation of T cells. Human PMN were incubated in cell culture medium in the absence or presence of an arginase inhibitor. T cells from healthy donors w…

In Vitro Modulation of P-Glycoprotein Activity by Euphorbia intisy Essential Oil on Acute Myeloid Leukemia Cell Line HL-60R

2021

Euphorbia species have a large spectrum of traditional medicinal uses. We tested the biological activities of the essential oil (EO) of Euphorbia intisy Drake in an acquired multidrug resistance leukemia model to assess whether the EO obtained by hydrodistillation of stems was able to reverse the resistant phenotype. HL-60R cell lines are characterized by the overexpression of P-glycoprotein (P-gp), inhibitors of apoptosis proteins (IAPs) and constitutive expression of NF-κB. EO chemical composition was determined by GC/MS analysis

A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology.

2015

Background: Na+/H+ exchanger-1 (NHE-1) is involved in pH regulation and is up-regulated in different malignancies. Activation of NHE-1 is one way for allowing cells to avoid intracellular acidification and protect them against apoptosis. Inhibitors of NHE-1 are able to decrease intracellular pH and induce apoptosis. Some statins can also act by partial inhibition of NHE-1. This review presents progress in understanding the mechanisms of action of these inhibitors, connections with certain genetic mutations and acquired treatment resistance, as well as new patents on them. Methods: A MEDLINE search for original and review articles using key terms, Na+/H+ exchanger, leukemia, cariporide, and …